Clinical Effect of Ultrasound-Guided Adductor Block on Postoperative Analgesia After Total Knee Replacement.

Objective: To explore the clinical effects of ultrasound-guided adductor block (UGAB) on postoperative analgesia after total knee replacement. Methods: From March 2022 to June 2022, 60 patients in the First Affiliated Hospital of Chongqing Medical University were included. They were divided into control (n = 30) and ultrasonic groups (n = 30). They all received total knee arthroplasty. Before total knee arthroplasty, patients in the control and ultrasonic groups underwent general anesthesia and UGAB, respectively. Visual Analogue Scale (VAS) was used to assess the pain. The time of the first straight leg elevation and the first landing time were recorded. Knee joint function was evaluated. Information about the dosage of tramadol intramuscular injection and the number of times patient-controlled analgesia pump pressing was collected. The serum levels of interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) were detected. Results: Compared with the control group, UGAB increased the rate of muscle contraction and relaxation and total and relaxation after total knee replacement in the ultrasonic group (P < .05). UGAB reduced VAS scores of pain during passive activity after operation (P < .05). UGAB also facilitated the first straight leg lifting time after the operation and the time of the first landing after the operation (P < .05). Meanwhile, UGAB reduced the dose of tramadol and press times of the self-control analgesia pump after operation (P < 0.05). UGAB also suppressed postoperative IL-6 and hs-CRP levels and increased postoperative joint range of motion (P < .05). Conclusion: UGAB promotes early recovery of knee function with high safety in patients undergoing total knee replacement, with reduced postoperative pain and inflammatory reaction.

Quality markers of Dajianzhong decoction based on multicomponent qualitative and quantitative analysis combined with network pharmacology and chemometric analysis.

INTRODUCTION: Dajianzhong decoction (DJZD), a classic famous prescription, has a long history of medicinal application. Modern studies have demonstrated its clinical utility in the treatment of postoperative ileus (POI). But none of the current quality evaluation methods for this compound is associated with efficacy. OBJECTIVES: This study aimed to identify the quality markers (Q-Markers) connected to the treatment of POI in DJZD. METHODOLOGY: Ultra-performance liquid chromatography quadrupole Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap-MS) was used to identify the main constituents in DJZD. Based on the qualitative results obtained by fingerprinting, chemical pattern recognition (CPR) was used to analyse the key components affecting the quality and finally to establish the network of the active ingredients in DJZD with POI. RESULTS: A total of 64 chemical components were detected. After fingerprint analysis, 13 common peaks were identified. The fingerprint similarity of 15 batches of samples ranged from 0.860 to 1.000. CPR analysis was able to categorically classify 15 batches of DJZD into two groups. And gingerenone A, methyl-6-gingerdiol, 6-gingerol, and hydroxy-ß-sanshool contributed to their grouping. Twelve common components interact with the therapeutic targets for treating POI. In addition, the mechanism of this prescription for treating POI may be related to the jurisdiction of the neurological system, the immunological system, and the inflammatory response. CONCLUSIONS: This integrated approach can accurately assess and forecast the quality of DJZD, presume the Q-Markers of DJZD for POI, and lay the foundation for studying the theoretical underpinnings and exploring the mechanism of DJZD in the treatment of POI.

Mechanism of andrographis paniculata on lung cancer by network pharmacology and molecular docking.

BACKGROUND: Traditional Chinese medicine (TCM) has been widely recognized and accepted worldwide to provide favorable therapeutic effects for cancer patients. As Andrographis paniculata has an anti-tumor effect, it might inhibit lung cancer. OBJECTIVE: The drug targets and related pathways involved in the action of Andrographis paniculata against lung cancer were predicted using network pharmacology, and its mechanism was further explored at the molecular level. METHODS: This work selected the effective components and targets of Andrographis paniculata against the Traditional Chinese Medicine System Pharmacology (TCMSP) database. Targets related to lung cancer were searched for in the GEO database (accession number GSE136043). The volcanic and thermal maps of differential expression genes were produced using the software R. Then, the target genes were analyzed by GO and KEGG analysis using the software R. This also utilized the AutoDock tool to study the molecular docking of the active component structures downloaded from the PubChem database and the key target structures downloaded from the PDB database, and the docking results were visualized using the software PyMol. RESULTS: The results of molecular docking show that wogonin, Mono-O-methylwightin, Deoxycamptothecine, andrographidine F_qt, Quercetin tetramethyl (3',4',5,7) ether, 14-deoxyandrographolide, andrographolide-19-ß-D-glucoside_qt and 14-deoxy-11-oxo-andrographolide were potential active components, while AKT1, MAPK14, RELA and NCOA1 were key targets. CONCLUSION: This study showed the main candidate components, targets, and pathways involved in the action of Andrographis paniculata against lung cancer.

A review of the botany, ethnopharmacology, phytochemistry, pharmacology, toxicology and quality of Anemarrhena asphodeloides Bunge.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizomes of Anemarrhena asphodeloides Bunge., belonging to the family Liliaceae, are named 'Zhi-mu' according to traditional Chinese medicine theory. It is a medicinal plant that has long been used as a tonic agent in various ethnomedicinal systems in East Asia, especially in China, and also for treating arthralgia, hematochezia, tidal fever, night sweats, cough, dry mouth and tongue, hemoptysis, etc. THE ARM OF THE REVIEW: The review aims to provide a systematic overview of botany, ethnopharmacology, phytochemistry, pharmacology, toxicology and quality control of Anemarrhena asphodeloides and to explore the future therapeutic potential and scientific potential of this plant. MATERIALS AND METHODS: A comprehensive literature search was performed on Anemarrhena asphodeloides using scientific databases including Web of Science, PubMed, Google Scholar, CNKI, Elsevier, SpringerLink, ACS publications, ancient books, Doctoral and master's Theses. Collected data from different sources was comprehensively summarised for botany, ethnopharmacology, phytochemistry, pharmacology, toxicology and quality control of Anemarrhena asphodeloides. RESULTS: A comprehensive analysis of the literature as mentioned above confirmed that the ethnomedical uses of Anemarrhena asphodeloides had a history of thousands of years in eastern Asian countries. Two hundred sixty-nine compounds have been identified from Anemarrhena asphodeloides, including steroidal saponins, flavonoids, phenylpropanoids, alkaloids, steroids, organic acids, polysaccharides, benzophenones and other ingredients. Studies have shown that the extracts and compounds from Anemarrhena asphodeloides have extensive pharmacological activities, such as nervous system activity, antitumour, anti-inflammatory, antidiabetic, antiosteoporotic, antiallergic, antiplatelet aggregation, antimicrobial, antiviral, anti-ageing, hair growth promoting, preventing cell damage, etc. Evaluating the quality and toxicity of Anemarrhena asphodeloides is essential to confirm its safe use in humans. CONCLUSION: Anemarrhena asphodeloides is widely used in traditional medicine and have diverse chemical constituents with obvious biological activities. Nevertheless, more studies should be carried out in animals and humans to evaluate the cellular and molecular mechanisms involved in its biological activity and confirm its safe use.

Physical and functional interactome atlas of human receptor tyrosine kinases.

Much cell-to-cell communication is facilitated by cell surface receptor tyrosine kinases (RTKs). These proteins phosphorylate their downstream cytoplasmic substrates in response to stimuli such as growth factors. Despite their central roles, the functions of many RTKs are still poorly understood. To resolve the lack of systematic knowledge, we apply three complementary methods to map the molecular context and substrate profiles of RTKs. We use affinity purification coupled to mass spectrometry (AP-MS) to characterize stable binding partners and RTK-protein complexes, proximity-dependent biotin identification (BioID) to identify transient and proximal interactions, and an in vitro kinase assay to identify RTK substrates. To identify how kinase interactions depend on kinase activity, we also use kinase-deficient mutants. Our data represent a comprehensive, systemic mapping of RTK interactions and substrates. This resource adds information regarding well-studied RTKs, offers insights into the functions of less well-studied RTKs, and highlights RTK-RTK interactions and shared signaling pathways.

[Advances in microbial synthesis of plant natural products].

Plant natural products are one of the main sources of small molecule drugs, nutraceuticals, cosmetics and fragrances, and play an important role in economy development. At present, the way of obtaining plant natural products mainly depends on direct extraction from plants, which is farm land occupying and time consuming. The contents of active ingredients in plants are usually low, and thus the production cost is high. By elucidating the biosynthetic pathways and reconstructing the pathways in microbial cells, plant natural products can be produced by fermentation using renewable raw materials. Microbial biosynthesis provides a new route for the supply of plant natural products. This review summarizes the research progress of microbial synthesis of terpenoids, flavonoids, phenylpropanoids and other important natural products of plants in Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences. Current research challenges and future prospects are also briefly discussed.

Effect of Pheretima aspergillum on reducing fibrosis: A systematic review and meta-analysis.

Background: Pheretima aspergillum (common name: Earthworm, Chinese name: dilong) has been used in traditional Chinese medicine for thousands of years. Recently, a few scientific studies have investigated the antifibrotic effects of Dilong extract (DE) and produced controversial results. We conducted a meta-analysis to make an informed decision on the antifibrotic effects of Dilong extract. Methods: The studies on antifibrotic effects of Dilong extract published until July 2022 in the scientific databases [PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), VIP database for Chinese Technical Periodicals, SinoMed and WanFang database] were reviewed. The RevMan 5.4.1 software was used for standardized mean difference (SMD) analysis. Two researchers independently reviewed all the studies, and their quality was assessed using the Cochrane risk of bias tool. Results: A total of 325 studies were found in the scientific databases; however, only 13 studies met the criteria for analysis. Dilong extract treatment was associated with antifibrotic effects via inhibiting the transforming growth factor beta 1 (TGF-ß1, SMD = -3.16, 95% CI: -4.18, -2.14, p < .00001) and alpha-smooth muscle actin (α-SMA: SMD = -2.57, 95% CI: -3.47, -1.66, p < .00001). Conclusion: Dilong extract effectively reduces tissue fibrosis; thus, further scientific studies should be conducted to investigate and develop it for clinical use. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022357141.

De Novo Biosynthesis of Polydatin in Saccharomyces cerevisiae.

Polydatin, with better structural stability and biological activities than resveratrol, is mainly extracted from the traditional Chinese medicinal plant Polygonum cuspidatum. In this study, based on the transcriptome analysis of P. cuspidatum, we identified the key glycosyltransferase of resveratrol and achieved the biosynthesis of polydatin from glucose by incorporation with the resveratrol biosynthesis module, UDP-glucose supply module, and glycosyltransferase expression module. Through metabolic engineering and fermentation optimization, the production of polydatin reached 545 mg/L, and the dry cell weight was 27.83 mg/g DCW, which was about twice that of extracted from the P. cuspidatum root (11.404 mg/g DCW). Therefore, it is possible to replace the production mode of polydatin from plant extraction to microbial chassis in the future.

Engineering microbial cell factories for the production of plant natural products: from design principles to industrial-scale production.

Plant natural products (PNPs) are widely used as pharmaceuticals, nutraceuticals, seasonings, pigments, etc., with a huge commercial value on the global market. However, most of these PNPs are still being extracted from plants. A resource-conserving and environment-friendly synthesis route for PNPs that utilizes microbial cell factories has attracted increasing attention since the 1940s. However, at the present only a handful of PNPs are being produced by microbial cell factories at an industrial scale, and there are still many challenges in their large-scale application. One of the challenges is that most biosynthetic pathways of PNPs are still unknown, which largely limits the number of candidate PNPs for heterologous microbial production. Another challenge is that the metabolic fluxes toward the target products in microbial hosts are often hindered by poor precursor supply, low catalytic activity of enzymes and obstructed product transport. Consequently, despite intensive studies on the metabolic engineering of microbial hosts, the fermentation costs of most heterologously produced PNPs are still too high for industrial-scale production. In this paper, we review several aspects of PNP production in microbial cell factories, including important design principles and recent progress in pathway mining and metabolic engineering. In addition, implemented cases of industrial-scale production of PNPs in microbial cell factories are also highlighted.

Statins and Metformin Use Is Associated with Lower PSA Levels in Prostate Cancer Patients Presenting for Radiation Therapy.

BACKGROUND: A possible association between the level of prostate specific antigen (PSA) and the use of some commonly prescribed medications has been reported in recent studies. Most of these studies were carried out in general populations of men who were screened for prostate cancer using the PSA test. We reported on the association between the initial PSA level and the use of statins, metformin and alpha-blockers in patients who were diagnosed with prostate cancer and presented for radiation therapy. METHODS: Three hundred and eighty one patients treated between the years of 2000-2005 and 2009-2012 were included in this retrospective study. The information about statin, metformin and alpha-blockers use was recorded immediately prior to treatment. Differences in PSA levels prior to treatment by medication status were estimated using univa-riate and multivariate linear regression on log PSA values. RESULTS: Compared with men who were not on these medications, the PSA level at presentation was 20% lower for statin users (p = 0.002) and 33% lower for metformin users (p = 0.004). We did not observe statistically significant associations between the use of statins or metformin and cancer stage, National Comprehensive Cancer Network (NCCN) risk score, or therapy outcome. A statistically significant association between the NCCN risk score and the use of alpha-blockers was observed (p = 0.002). CONCLUSIONS: We found that statins and metformin were associated with lower PSA levels in prostate cancer patients to an extent that could influence management decisions. We found no statistically significant associations between the use of these medications and treatment outcomes.

Production of salidroside in metabolically engineered Escherichia coli.

Salidroside (1) is the most important bioactive component of Rhodiola (also called as "Tibetan Ginseng"), which is a valuable medicinal herb exhibiting several adaptogenic properties. Due to the inefficiency of plant extraction and chemical synthesis, the supply of salidroside (1) is currently limited. Herein, we achieved unprecedented biosynthesis of salidroside (1) from glucose in a microorganism. First, the pyruvate decarboxylase ARO10 and endogenous alcohol dehydrogenases were recruited to convert 4-hydroxyphenylpyruvate (2), an intermediate of L-tyrosine pathway, to tyrosol (3) in Escherichia coli. Subsequently, tyrosol production was improved by overexpressing the pathway genes, and by eliminating competing pathways and feedback inhibition. Finally, by introducing Rhodiola-derived glycosyltransferase UGT73B6 into the above-mentioned recombinant strain, salidroside (1) was produced with a titer of 56.9 mg/L. Interestingly, the Rhodiola-derived glycosyltransferase, UGT73B6, also catalyzed the attachment of glucose to the phenol position of tyrosol (3) to form icariside D2 (4), which was not reported in any previous literatures.

Characteristics of Se-enriched mycelia by Stropharia rugoso-annulata and its antioxidant activities in vivo.

Selenium (Se) is an essential trace element for humans and animals. Stropharia rugoso-annulata is a nutritional and functional mushroom containing many kinds of bioactive ingredients. The aims of this study were to investigate the Se-enrichment characteristics of S. rugoso-annulata in submerged culture and evaluate the antioxidant activities of Se-enriched mycelia in vivo in terms of the values of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and malondialdehyde (MDA). The optimum parameters of Se-enrichment under the optimal Se concentration (150 microg/mL) in media were as follows: biomass 8.11 +/- 0.25 g/L, Se content in mycelia 4,727.68 +/- 13 microg/g, Se-accumulated rate 24.68 +/- 1.67%, and percentage of organic Se 96.27 +/- 3.26%. The mainly subsistent forms of selenium in Se-enriched mycelia were selenoprotein and selenium-polysaccharide. The contents of total amino acids (TAA) and essential amino acids (EAA) in Se-enriched mycelia were increased by 13.5 +/- 1.09% and 12.8 +/- 0.89%, respectively. It was efficient for Se-enriched mycelia to elevate GSH-Px and SOD activities and decrease MDA content. These results indicated that Se-enriched mycelia of S. rugoso-annulata represent a novel dietary source of bioavailable supplemental selenium.

[Protective effect of shenfu injection against ischemia-reperfusion injury due to pancreas transplantation in rats].

OBJECTIVE: To investigate the protective effect of Shenfu Injection against ischemia-reperfusion (I/R) injury due to pancreas transplantation in rats, and explore its possible mechanism. METHODS: Six normal SD rats with sham operation were taken as the normal control group, 24 steptozozin-induced diabetic SD rats were randomly divided into 4 groups, with 6 in each group. Except I/R group, the rats in the other groups were intravenous injected with Shenfu Injection (SF,10 mg/kg), Hongshen Injection (HS, 9 mg/kg) and Fuzi Injection (FZ 1 mg/kg) respectively at the day and 30 minutes before pancreas transplantation performed in the SF group, HS group and FZ group, respectively. At the same time, rats in the normal control group and in the I/R group were intravenously injected the same volume of normal saline. The blood glucose was detected before and after reperfusion, and 2 hours later after reperfusion, the contents of serum nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha), the concentrations of malondialdehyde (MDA) , superoxide dismutase (SOD) , and myeloperoxidase (MPO) in the transplanted pancreas tissues were detected. The cell apoptosis of the transplanted pancreas tissue was determined by TUNEL, and the bcl-2 and Bax protein expression was determined by Western blot. RESULTS: After reperfusion, the levels of blood glucose and TNF-alpha decreased and the concentration of NO increased in the SF group, HS group and FZ group, compared with those in the I/R group. The activity of SOD, bcl-2 expression and the ratio of bcl-2 and Bax were higher, while the content of MDA, the activity of MPO, apoptotic indexes, and Bax expression were lower in the SF group, HS group and FZ group than those in the I/R group. CONCLUSION: Shenfu Injection can protect L/R injury due to pancreas transplantation in rats, the possible mechanism may be related to promoting activity of SOD, increasing synthesis of endogenous NO, decreasing the excretion of TNF-alpha, alleviating conglutination and aggregation of polymorphonuclear neutrophils (PMNs) in pancreas, as well as up-regulating Bcl-2 gene expression and down-regulating the Bax gene expression.